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Bone resorption in syndromes of the Ras/MAPK pathway
Author(s) -
Stevenson DA,
Schwarz EL,
Carey JC,
Viskochil DH,
Hanson H,
Bauer S,
Cindy Weng HY,
Greene T,
Reinker K,
Swensen J,
Chan RJ,
Yang FC,
Senbanjo L,
Yang Z,
Mao R,
Pasquali M
Publication year - 2011
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01619.x
Subject(s) - deoxypyridinoline , pyridinoline , bone resorption , endocrinology , medicine , mapk/erk pathway , bone remodeling , resorption , osteoporosis , chemistry , signal transduction , biochemistry , osteocalcin , alkaline phosphatase , enzyme
Stevenson DA, Schwarz EL, Carey JC, Viskochil DH, Hanson H, Bauer S, Cindy Weng H‐Y, Greene T, Reinker K, Swensen J, Chan RJ, Yang F‐C, Senbanjo L, Yang Z, Mao R, Pasquali M. Bone resorption in syndromes of the Ras/MAPK pathway. Disorders of the Ras/mitogen‐activated protein kinase (MAPK) pathway have an overlapping skeletal phenotype (e.g. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and neurofibromatosis type 1 (NF1) individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine‐derived crosslinks of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Participants were individuals with Noonan syndrome ( n = 14), Costello syndrome ( n = 21), and cardiofaciocutaneous (CFC) syndrome ( n = 14). Pyridinium crosslinks from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by high performance liquid chromatography. Three separate analyses of covariance were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. The Dpd and the Dpd/Pyd ratio were elevated (p < 0.0001) in all three conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis.